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There is little data regarding the risks and benefits of bariatric surgery in patients with coronary artery disease (CAD). We aimed to assess the short- and long-term cardiovascular outcomes of patients with CAD undergoing bariatric surgery. Patients with a history of CAD were identified from a dedicated database with prospectively collected outcomes, comprising all 6795 patients who underwent bariatric surgery between January 1992 and October 2017. Patients were matched with patients who did not have CAD before the bariatric surgery procedure. The primary endpoints were mortality (cardiac and noncardiac) and major adverse cardiocerebral events (MACCE), including all-cause death, myocardial infarction, stroke, and myocardial revascularization at 30 days after bariatric surgery and throughout follow-up. After propensity score matching, 249 patients with chronic CAD were matched with 249 patients without CAD. Throughout follow-up (7.4 years; interquartile range 4.1 to 11.5, maximum 22 years), mortality (mainly cardiac mortality) remained significantly higher in the CAD compared with the non-CAD group (18% vs 10%, hazard ratio [HR] 1.70, 95% confidence interval [CI]: 1.03 to 2.79, p = 0.037). At 30 days, MACCE rate was significantly higher in the CAD compared with the non-CAD group (3.6% vs 0.4%, p = 0.011), essentially driven by non-ST elevation myocardial infarctions. After 30 days, MACCE rates remained significantly higher in the CAD group (30% vs 14%, HR 2.18, 95% CI: 1.45-3.28, p = 0.0002). In conclusion, patients with severe obesity and CAD referred to bariatric surgery were at a higher risk of early and late MACCE compared with non-CAD severely obese patients. Further study is required to define how this cardiovascular risk compares with nonoperated patients.

Semicarbazide-sensitive amine oxidase (SSAO), identical to primary amine oxidase or vascular adhesion protein-1, is a membrane enzyme that generates hydrogen peroxide. SSAO is highly expressed at the adipocyte surface, and its plasma levels increase with type 2 diabetes. Since visceral adipose tissue (AT) is more tightly associated with obesity complications than subcutaneous (SC) abdominal fat, we compared SSAO activity in plasma and 4 distinct AT locations in 48 severely obese women (body mass index (BMI), averaging 54 ± 11 kg/m2), with or without a dysmetabolic profile. Higher glucose and triacylglycerol levels vs lower high-density lipoprotein (HDL)-cholesterol characterized dysmetabolic women (DYS; n = 25) from non-dysmetabolic (NDYS; n = 23), age- and weight-matched subjects. SC, mesenteric (ME), omental (OM), and round ligament (RL) fat locations were collected during bariatric surgery. SSAO capacity to oxidize up to 1 mM benzylamine was determined in AT and plasma with radiometric and fluorimetric methods. Plasma SSAO was higher in the DYS group. SSAO activity was higher in fat than in plasma, when expressed as radiolabeled benzaldehyde per milligram of protein. In ATs from DYS women, protein content was 10 % higher, and basal hydrogen peroxide release lower than in NDYS subjects, except for RL location. The SSAO affinity towards benzylamine did not exhibit regional variation and was not altered by a dysmetabolic profile (Km averaging 184 ± 7 μM; n = 183). Although radiometric and fluorimetric methods gave different estimates of oxidase activity, both indicated that AT SSAO activity did not vary according to anatomical location and/or metabolic status in severely obese women.

OBJECTIVEDiabesity during gestation predisposes offspring to lifetime cardiometabolic risk. We demonstrated that maternal biliopancreatic diversion surgery (BPD) improved metabolic fitness and pregnancies reducing cardiometabolic risk in siblings born after (AMS) compared to before maternal surgery (BMS). We found differential methylation of inflammatory and glucoregulatory genes in peripheral blood cell DNA in offspring and in mothers after BPD compared to preoperative “control” women. Here we study offspring trajectories of cardiometabolic risk markers and determine persistence of the methylome related to body weight (BMI) and gestational weight gain (GWG).RESEARCH DESIGN AND METHODSProspective, cross-sectional study of 133 mothers with 89 BMS and 183 AMS offspring born mean 4 years after BPD and 83 unoperated control women was conducted, and differential methylation patterns in mothers were compared with those of offspring during 2-26 years.RESULTSIndependent of maternal or offspring BMI and GWG, postoperative maternal metabolic fitness was associated with improved cardiometabolic phenotype in AMS vs. BMS offspring sustained beyond puberty. BMS offspring exhibited increasing linear trajectories of weight, cardiometabolic and inflammation risk factorsversusnormative horizontal trajectories of AMS offspring. Methylation differences between AMS and BMS offspring identified 45 625 differentially methylated sites, 73% overlapping with those of mothers vs. controls; 4 446 demonstrated similar sustained directionality of differences in methylation levels; 154 sites exhibited significant correlation coefficients (r≥0.4) overrepresented within genes associated with cardiometabolic risk, growth and inflammation.CONCLUSIONMaternal BPD appears to epigenetically prevent transmission of cardiometabolic risk independent of BMI.

This chapter summarizes the early postoperative and long-term complications of biliopancreatic diversion with duodenal switch (BPD-DS) procedures. Perioperative mortality for BPD-DS is currently around 0.1%, with an early complication rate of 7%. The standard follow-up required for the prevention of nutritional deficiencies as well as the management of short- and long-term complications specific to metabolic surgeries are also discussed. The data and clinical views expressed in this chapter are based to a large extent on the authors’ experience with 5,000 BPD-DS surgeries in our institution over the last 25 years, and which have been reported extensively in the literature. In our experience, severe protein malnutrition occurred in 10% patients, of whom 5% required readmission and 1.5% a surgical revision to correct the problem.

Gene expression (qPCR) was compared in round ligament (RL), omental (OME) and mesenteric (MES) ATs from 48 severely obese women (BMI, 54±11 kg/m(2); 38±9 yrs). The mRNA levels of enzymes of lipid metabolism (LPL, HSL, and PDE-3B), cortisol production (11βHSD-1), adipogenesis (PPAR-γ1/2), thrombosis and inflammation (PAI-1, IL-6, TNF-α and adiponectin) were determined. AT-LPL mRNA was highest in RL. The highest PDE-3B and lowest PAI-1 mRNA levels were observed in RL and MES. The lowest IL-6 and TNF-α and the highest adiponectin and PPAR-g1/2 mRNA levels were found in RL AT. 11βHSD-1 was highest in RL and OME. A higher lipogenic and adipogenic, and lower pro-inflammatory and pro-thrombotic profiles of the RL suggest a lesser deleterious impact on obesity-related complications.

Biliopancreatic diversion (BPD) is a complex bariatric operation requiring meticulous surveillance which has impeded its broad adoption. Improvements in surgical care and technique, better teaching programs, and stringent norms for follow-up have contributed to increased safety of BPD for patients with BMI

Biliopancreatic nbsp nbsp nbsp diversion nbsp nbsp nbsp with nbsp nbsp nbsp duodenal nbsp nbsp nbsp switch nbsp nbsp nbsp BPD DS is nbsp a surgical nbsp intervention known to induce substantial weight loss and significant long lasting metabolic nbsp improvements nbsp including nbsp a nbsp decrease nbsp in nbsp insulin nbsp resistance nbsp IR nbsp and resolution of type diabetes T D The specific mechanisms by which metabolic improvements occur after BPD DS are still not fully elucidated and the impact of BPD DS on gene methylation profiles has not been studied To gain understanding of epigenetic factors that may predispose to metabolic improvements after weight loss nbsp surgery nbsp we nbsp characterized nbsp the nbsp methylation nbsp signature nbsp of nbsp genes nbsp associated nbsp to nbsp T D nbsp and nbsp IR nbsp after nbsp BPD DS nbsp Most nbsp of nbsp the nbsp genes nbsp involved nbsp in nbsp T D nbsp and nbsp IR nbsp pathways nbsp exhibited nbsp significant nbsp differences nbsp in nbsp methylation nbsp levels nbsp after nbsp BPD DS nbsp compared nbsp to nbsp a nbsp pre surgery nbsp control nbsp group nbsp The nbsp majority nbsp of nbsp these nbsp loci nbsp were nbsp significantly nbsp hypomethylated nbsp suggesting nbsp an nbsp effect nbsp of nbsp bariatric nbsp surgery nbsp on nbsp the nbsp epigenetic nbsp signature of genes encoding proteins involved in glucose homeostasis

SummaryObjective Sex steroid hormones play an important regulatory role in fat metabolism and obesity. We hypothesized involvement of interactions between ovarian hormones with acylation stimulating protein (ASP). Design, patients and measurements In 392 women with wide age (18–69 years) and body size (BMI: 17 to 90 kg/m2) ranges, fasting plasma levels of ASP, ovarian hormones, glucose, adiponectin and lipids/apolipoproteins were assessed, along with determination of metabolic syndrome (MS) features. Gene expression of C3 (ASP precursor) and related receptors C5L2, C3aR and C5aR in subcutaneous and omental adipose tissues was measured in a subset. Results Acylation stimulating protein correlated negatively with concentrations of estradiol (P

Objective— Animal models have evidenced the role of intestinal triglyceride-rich lipoprotein overproduction in dyslipidemia. However, few studies have confronted this issue in humans and disclosed the intrinsic mechanisms. This work aimed to establish whether intestinal insulin resistance modifies lipid and lipoprotein homeostasis in the intestine of obese subjects. Approach and Results— Duodenal specimens obtained from 20 obese subjects undergoing bariatric surgery were paired for age, sex, and body mass index with or without insulin resistance, as defined by the homeostasis model assessment of insulin resistance. Insulin signaling, biomarkers of inflammation and oxidative stress, and lipoprotein assembly were assessed. The intestine of insulin-resistant subjects showed defects in insulin signaling as demonstrated by reduced protein kinase B phosphorylation and increased p38 mitogen-activated protein kinase phosphorylation, likely as the result of high oxidative stress (evidenced by malondialdehyde and conjugated dienes) and inflammation (highlighted by nuclear factor-κB, tumor necrosis factor-α, interleukin-6, intercellular adhesion molecule-1, and cyclooxygenase-2). Enhanced de novo lipogenesis rate and apolipoprotein B-48 biogenesis along with exaggerated triglyceride-rich lipoprotein production were observed, concomitantly with the high expression levels of liver and intestinal fatty acid–binding proteins and microsomal transfer protein. The presence of an aberrant intracellular cholesterol transport/metabolism was also suggested by the reduced expression of ATP-binding cassette A1 transporter and proprotein convertase subtilisin/kexin type 9. Conclusions— According to the present data, the small intestine may be classified as an insulin-sensitive tissue. Dysregulation of intestinal insulin signaling, possibly triggered by oxidative stress and inflammation, was associated with exaggerated lipogenesis and lipoprotein synthesis, which may represent a key mechanism for atherogenic dyslipidemia in patients with metabolic syndrome.

DNA methylation has been mostly studied in circulating blood cells. Although being readily accessible, metabolically active tissues such as adipose tissue would be more informative for the study of metabolic disorders. However, whether or not the blood DNA methylation profile correlates with that of adipose tissue remains unknown. In this study, DNA methylation patterns of variation at LEP and ADIPOQ gene loci were similar between individual CpGs across the different tissues. We also report that DNA methylation levels at biologically relevant CpGs are correlated between blood, subcutaneous, and visceral adipose tissue, and that these nearby CpGs are associated with LEP and ADIPOQ gene expression in adipose tissues. These results will be highly relevant for future epigenetic studies in metabolic disorders.

Obesity and overnutrition during pregnancy affect fetal programming of adult disease. Children born after maternal bariatric gastrointestinal bypass surgery (AMS) are less obese and exhibit improved cardiometabolic risk profiles carried into adulthood compared with siblings born before maternal surgery (BMS). This study was designed to analyze the impact of maternal weight loss surgery on methylation levels of genes involved in cardiometabolic pathways in BMS and AMS offspring. Differential methylation analysis between a sibling cohort of 25 BMS and 25 AMS (2–25 y-old) offspring from 20 mothers was conducted to identify biological functions and pathways potentially involved in the improved cardiometabolic profile found in AMS compared with BMS offspring. Links between gene methylation and expression levels were assessed by correlating genomic findings with plasma markers of insulin resistance (fasting insulin and homeostatic model of insulin resistance). A total of 5,698 genes were differentially methylated between BMS and AMS siblings, exhibiting a preponderance of glucoregulatory, inflammatory, and vascular disease genes. Statistically significant correlations between gene methylation levels and gene expression and plasma markers of insulin resistance were consistent with metabolic improvements in AMS offspring, reflected in genes involved in diabetes-related cardiometabolic pathways. This unique clinical study demonstrates that effective treatment of a maternal phenotype is durably detectable in the methylome and transcriptome of subsequent offspring.

Background. Maternal obesity, excess weight gain and overnutrition during pregnancy increase risks of obesity, type 2 diabetes mellitus, and cardiovascular disease in the offspring. Maternal biliopancreatic diversion is an effective treatment for severe obesity and is beneficial for offspring born after maternal surgery (AMS). These offspring exhibit lower severe obesity prevalence and improved cardiometabolic risk factors including inflammatory marker compared to siblings born before maternal surgery (BMS).Objective. To assess relationships between maternal bariatric surgery and the methylation/expression of genes involved in the immune and inflammatory pathways.Methods. A differential gene methylation analysis was conducted in a sibling cohort of 25 BMS and 25 AMS offspring from 20 mothers. Following differential gene expression analysis (23 BMS and 23 AMS), pathway analysis was conducted. Correlations between gene methylation/expression and circulating inflammatory markers were computed.Results. Five immune and inflammatory pathways with significant overrepresentation of both differential gene methylation and expression were identified. In the IL-8 pathway, gene methylation correlated with both gene expression and plasma C-reactive protein levels.Conclusion. These results suggest that improvements in cardiometabolic risk markers in AMS compared to BMS offspring may be mediated through differential methylation of genes involved in immune and inflammatory pathways.

In the past 10 years, most bariatric surgeries have seen an important reduction in the early complication rate, partly associated with the development of the laparoscopic approach. Our objective was to assess the current early complication rate associated with biliopancreatic diversion with duodenal switch (BPD-DS) since the introduction of a laparoscopic approach in our institution, a university-affiliated tertiary care center.A consecutive series of 1000 patients who had undergone BPD-DS from November 2006 to January 2010 was surveyed. The primary endpoint was the mortality rate. The secondary endpoints were the major 30-day complication rate and hospital stay10 days. The data are reported as a mean ± SD, comparing the laparoscopic (n = 228) and open (n = 772) groups.The mean age of the patients was 43 ± 10 years (40 ± 10 years in the laparoscopy group versus 44 ± 10 years in the open group, P.01). The preoperative body mass index was 51 ± 8 kg/m(2) (47 ± 7 laparoscopy versus 52 ± 8 kg/m(2) open, P.01). The conversion rate in the laparoscopy group was 2.6%. There was 1 postoperative death (.1%) from a pulmonary embolism in the laparoscopy group. The mean hospital stay was shorter after laparoscopic surgery (6 ± 6 d versus 7 ± 9 d, P = .01), and a hospital stay10 days was more frequent in the open group (4.4% versus 7%, P = .04). Major complications occurred in 7% of the patients, with no significant differences between the 2 groups (7% versus 7.4%, P = .1). No differences were found in the overall leak or intra-abdominal abscess rate (3.5% versus 4%, P = .1); however, gastric leaks were more frequent after open surgery (0% versus 2%, P = .02). During a mean 2-year follow-up, 1 additional death occurred from myocardial infarction, 2 years after open BPD-DS.The early and late mortality rate of BPD-DS is low and comparable to that of other bariatric surgeries.

International audience; Piceatannol is a hydroxylated derivative of resveratrol. While both dietary polyphenols coexist in edible plants and fruits, and share equivalent concentrations in several wines, the influence of piceatannol on adiposity has been less studied than that of resveratrol. Though resveratrol is now recognized to limit fat deposition in various obesity models, the benefit of its dietary supplementation remains under debate regarding human obesity treatment or prevention. The research for more potent resveratrol analogs is therefore still undergoing. This prompted us to compare various effects of piceatannol and resveratrol directly on human adipose tissue (hAT). Hydrogen peroxide release was measured by Amplex Red-based fluorescence in subcutaneous hAT samples from obese patients. Interactions of stilbenes with human amine oxidases and quinone reductase were assessed by radiometric methods, computational docking and electron paramagnetic resonance. Influences on lipogenic and lipolytic activities were compared in mouse adipocytes. Resveratrol and piceatannol inhibited monoamine oxidase (MAO) with respective IC50 of 18.5 and 133.7 μM, but not semicarbazide-sensitive amine oxidase (SSAO) in hAT. For both stilbenes, the docking scores were better for MAO than for SSAO. Piceatannol and resveratrol similarly hampered hydrogen peroxide detection in assays with and without hAT, while they shared pro-oxidant activities when incubated with purified quinone reductase. They exhibited similar dose-dependent inhibition of adipocyte lipogenic activity. Only piceatannol inhibited basal and stimulated lipolysis when incubated at a dose ≥100 μM. Thus, piceatannol exerted on fat cells dose-dependent effects similar to those of resveratrol, except for a stronger antilipolytic action. In this regard, piceatannol should be useful in limiting the lipotoxicity related to obesity when ingested or administered alone - or might hamper the fat mobilization induced by resveratrol when simultaneously administered with it.

Background The TOMM20 gene was previously identified as differentially expressed and methylated between severely obese subjects with and without metabolic syndrome (MS). Since metabolic complications do not affect all obese patients to the same extent, the aim of this study was to identify methylation quantitative trait loci (meQTL) potentially associated with MS-related complications within the TOMM20 locus. Methods Methylation profiling, SNP genotyping and meQTL association tests (general linear models) were performed in a population of 48 severely obese subjects. Genotyping was extended to a larger population of 1720 severely obese subjects with or without MS, where genotype- and diplotype-based association tests were assessed by logistic regression. In silico analyses were performed using TRAP. Results Four SNPs were identified as significant meQTLs for the differentially methylated site cg16490124. Individuals carrying rare alleles of rs4567344 (A > G) (P = 4.9 × 10−2) and rs11301 (T > C) (P = 5.9 × 10−3) showed decreased methylation levels at this site, whereas those carrying rare alleles of rs4551650 (T > C) (P = 3.5 × 10−15) and rs17523127 (C > G) (P = 3.5 × 10−15) exhibited a significant increase in methylation. rs4567344 and rs11301 were associated with increased susceptibility to exhibit high plasma triglycerides (TG ≥ 1.69 mmol/L), while rare alleles of rs4551650 and rs17523127 were significantly more represented in the low plasma total-C group (total-C ≤ 6.2 mmol/L). Haplotype reconstruction with the four meQTLs (rs4567344, rs11301, rs4551650, rs17523127) led to the identification of ten different diplotypes, with H1/H2 (GCGG/ACGG) exhibiting a nearly absence of methylation at cg16490124, and showing the highest risk of elevated plasma TG levels [OR = 2.03 (1.59–3.59)], a novel association with elevated LDL-cholesterol [OR = 1.86 (1.06–3.27)] and the complete inversion of the protective effect on total-C levels [OR = 2.03 (1.59–3.59)], especially in men. In silico analyses revealed that rs17523127 overlapped the CpG site cg16490124 and encompassed the core binding sites of the transcription factors Egr 1, 2 and 3, located within the TOMM20 promoter region. Conclusion This study demonstrates that TOMM20 SNPs associated with MS-related lipid alterations are meQTLs potentially exerting their action through a CpG methylation-dependent effect. The strength of the diplotype-based associations may denote a novel meQTL additive action and point to this locus as particularly relevant in the inter-individual variability observed in the metabolic profiles of obese subjects. Electronic supplementary material The online version of this article (doi:10.1186/s13098-016-0171-3) contains supplementary material, which is available to authorized users.

The majority of bariatric surgeries in Canada are performed in women of reproductive age. Clinicians encounter more and more often pregnancies that occur after bariatric surgeries. The appropriate management and education of women who want to conceive after bariatric surgery is still unclear due to the lack of consistent data about maternal and neonatal outcomes following bariatric surgery. Maternal obesity during pregnancy confers a higher risk for gestational diabetes, hypertensive disorders, congenital malformations, prematurity and perinatal mortality. Generally, pregnancies in severely obese women who have undergone bariatric surgery are safe, and the women are at significantly lower risk for gestational diabetes, hypertensive disorders and large-for-gestational-age neonates, but the surgery confers a higher risk for small-for-gestational-age infants and prematurity. This review aims to provide evidence from recent publications about the risks and benefits of bariatric surgeries in the context of future pregnancies.

Additional file 1: Table S1. Genotype distribution of genotyped and imputed SNPs within the TOMM20 locus. Figure S1. Sequence logos are the graphical representation of the Egr1 (a), Egr2 (b) and Egr3 (c) position-specific scoring matrix (PSSM) identified by TRAP and obtained from the Transfac database (IDs: M00243, M00245 and M00246, respectively). Sequence logo shows the base preference, sized and sorted relative to their occurrence in the PSSM.

Epigenetic mechanisms are known to be involved in tissue-specific differentiation. DNA methylation patterns have been shown to be largely conserved across tissues but with variation for specific genes. However, it is unclear whether the variability observed in the methylation profile of a metabolically active tissue is reflected in other sources such as hematopoietic tissue. This study aimed to test blood genome-wide CpG site methylation levels as a surrogate model for visceral adipose tissue (VAT) methylation and to verify whether it appropriately reflects differences in methylation levels found in VAT between men discordant for the metabolic syndrome (MetS). Tissue specimens (VAT and blood samples) were obtained from 16 severely obese individuals discordant for the MetS. CpG sites methylation levels were measured with the Infinium HumanMethylation450 BeadChip and correlations of methylation levels between VAT and blood were computed. Differences in methylation levels between individuals with and without MetS were tested in both tissues. Pathway analysis was conducted for differentially methylated CpG sites common to both tissues. High cross-tissue correlations were observed for VAT and blood (0.952±0.014) while some CpG sites had significantly different methylation levels in VAT versus blood. Differential methylation analysis between individuals with and without MetS demonstrated a higher number of differentially methylated CpG sites in VAT than in blood (11,778 vs. 881, respectively) with nearly 4% of differentially methylated sites found in VAT being also represented in blood. Common differentially methylated sites were involved in inflammatory-, lipid- and diabetes-related pathways. These results suggest that blood methylation levels of specific CpG sites may adequately reflect VAT methylation levels for some of the MetS-related genes, specifically for inflammatory, lipid and glucose metabolism genes.

The biliopancreatic diversion surgery with duodenal switch (BPD-DS) is a surgical procedure that not only induces significant weight loss, but also promotes remission of diabetes. However, the mechanism responsible for this insulin-potentiating effect (both on sensitivity and production) is not yet clearly understood. The insulin-like growth factor (IGF) binding protein 2 (IGFBP-2) is a 36 kDa circulating protein that has been recently suggested to modulate insulin sensitization and fat accumulation. In humans, a low-circulating concentration of IGFBP-2 has been associated with obesity and insulin resistance. We thus tested the hypothesis that BPD-DS would trigger an increase in IGFBP-2 levels. Plasma IGFBP-2 was quantified by enzyme-linked immunosorbent assay in 77 severely obese men and women before and up to 1 year after BPD-DS surgery. Baseline IGFBP-2 levels were 159 ± 17 ng/ml. Plasma IGFBP-2 levels increased significantly as soon as 24 h after BPD-DS surgery and were further augmented at both 6 months and 1 year after the surgery, reaching 748 ± 65 ng/ml. Changes in IGFBP-2 concentrations were significantly and negatively associated with blood glucose, insulin, triglycerides, and total cholesterol levels. The present findings suggest that the rise in IGFBP-2 levels is associated with the improvements in glucose and lipid metabolism in the short- and long-term after BPD-DS. The mechanisms for the augmentation in IGFBP-2 after BPD-DS and its contribution to insulin sensitization remain to be elucidated.

Adipogenesis and lipid storage in human adipose tissue are inhibited by androgens such as DHT. Inactivation of DHT to 3α-diol is stimulated by glucocorticoids in human preadipocytes. We sought to characterize glucocorticoid-induced androgen inactivation in human preadipocytes and to establish its role in the antiadipogenic action of DHT. Subcutaneous and omental primary preadipocyte cultures were established from fat samples obtained in subjects undergoing abdominal surgeries. Inactivation of DHT to 3α/β-diol for 24 h was measured in dexamethasone- or vehicle-treated cells. Specific downregulation of aldo-keto reductase 1C (AKR1C) enzymes in human preadipocytes was achieved using RNA interference. In whole adipose tissue sample, cortisol production was positively correlated with androgen inactivation in both subcutaneous and omental adipose tissue ( P < 0.05). Maximal dexamethasone (1 μM) stimulation of DHT inactivation was higher in omental compared with subcutaneous fat from men as well as subcutaneous and omental fat from women ( P < 0.05). A significant positive correlation was observed between BMI and maximal dexamethasone-induced DHT inactivation rates in subcutaneous and omental adipose tissue of men and women ( r = 0.24, n = 26, P < 0.01). siRNA-induced downregulation of AKR1C2, but not AKR1C1 or AKR1C3, significantly reduced basal and glucocorticoid-induced androgen inactivation rates ( P < 0.05). The inhibitory action of DHT on preadipocyte differentiation was potentiated following AKR1C2 but not AKR1C1 or AKR1C3 downregulation. Specifically, lipid accumulation, G3PDH activity, and FABP4 mRNA expression in differentiated preadipocytes exposed to DHT were reduced further upon AKR1C2 siRNA transfection. We conclude that glucocorticoid-induced androgen inactivation is mediated by AKR1C2 and is particularly effective in omental preadipocytes of obese men. The interplay between glucocorticoids and AKR1C2-dependent androgen inactivation may locally modulate adipogenesis and lipid accumulation in a depot-specific manner.

Obese individuals are characterized by a chronic, low-grade inflammatory state. Increased levels of C-reactive protein (CRP), a marker of inflammation, have been observed in subjects with the metabolic syndrome. We have previously reported that genes encoding proteins involved in the anti-inflammatory and immune response are differentially expressed in visceral adipose tissue of obese men with or without the metabolic syndrome. Among these genes, the interferon-gamma-inducible protein 30 (IFI30), CD163 molecule (CD163), chemokine (C-X-C motif) ligand 9 (CXCL9) and thymic stromal lymphopoietin (TSLP), were selected for further genetic analyses. The aim of the study was to verify whether IFI30, CD163, CXCL9 and TSLP gene polymorphisms contribute to explain the inter-individual variability of the inflammatory profile of obesity assessed by plasma high-sensitivity CRP concentrations. A total of 1185 severely obese individuals were genotyped for single nucleotide polymorphisms (SNPs) covering most of the sequence-derived genetic variability at the IFI30, CD163, CXCL9 and TSLP gene loci (total of 27 SNPs). Following measurement of plasma CRP levels, subjects were divided into two groups, low vs. high using the median value of plasma CRP levels (8.31 mg/L) as a cutoff point. Genotype frequencies were compared between groups. Associations between genotypes and plasma CRP levels (continuous variable) were also tested after adjustments for age, sex, smoking and BMI. The rs11554159 and rs7125 IFI30 SNPs showed a significant difference in genotype frequencies (p

Background Biliopancreatic diversion with duodenal switch (DS) has been the standard surgical approach for the treatment of morbidly obese patients at our institution since the early 1990s. The published data, however, have shown the use of the DS to be limited to the treatment of super-morbidly obese patients (body mass index [BMI] ≥50 kg/m 2 ). The aim of the present study was to present our long-term results with the DS in patients with an initial BMI of 2 . Methods This was a retrospective study of all patients with a BMI 2 who had undergone DS from June 1992 to May 2005. The data are reported as the mean ± standard deviation. Results The data from 810 consecutive patients, with a mean initial BMI of 44.2 ± 3.6 kg/m 2 , were reviewed. The mean follow-up was 103 ± 49 months. Major perioperative complications occurred in 5.8% of patients, including 5 deaths (.6%). The initial excess weight loss was 76% ± 22%, and the excess weight loss was >50% in 89% of patients. Malnutrition required readmission in 4.3% and surgical revision in 1.5%. The prevalence of severe albumin deficiency ( Conclusion These results showed that in non super-obese patients, DS was very efficient in terms of weight loss and patient satisfaction. This was associated with a 1.5% risk of revision for malnutrition. However, nutritional deficiencies required frequent readjustment of supplements, particularly for calcium, vitamin A, and vitamin D.

Overweight individuals sway more than normal weight individuals. Major weight loss improves their balance control despite a related decrease in muscle strength. Presumably, muscular strength is an important factor for balance control. This study investigated the effect that a change in body mass has on relative strength and balance control.Force (isometric knee extension) and balance control (center of pressure speed and range) were studied in three groups; normal weight (BMI25 kg m(-2)), obese (30 kg m(-2)BMI40 kg m(-2)) and excess obese (BMI40 kg m(-2)) Caucasian male individuals.The excess obese individuals who underwent bariatric surgery as a weight loss strategy were studied before, 3 and 12 months after losing on average, 66.9 kg (+/-95% CI 55.8, 77.9 kg; on average, 45% of their weight). The obese individuals who underwent diet modifications were studied before dieting and when resistance to weight loss occurred after losing on average 11.7 kg (+/-95% CI 9.3, 14.2 kg; on average, 12% of their weight). The control group was studied twice, 50 weeks apart. In obese and excess obese individuals, losing weight reduced absolute knee muscular strength on average, by 8.2 kg (+/-95% CI 3.9, 12.5 kg; on average, 10% of their strength) and 23.9 kg (+/-95% CI 12.1, 35.8 kg; on average, 33% of their strength). However, it also increased balance control measured with speed of the center of foot pressure, on average, by 0.10 cm s(-1) (+/-95% CI 0.05, 0.14 cm s(-1); or increased of 12%) and 0.28 cm s(-1) (+/-95% CI 0.07, 0.47 cm s(-1); increased of 27%), respectively. Relative strength increased approximately by 22% for only the excess obese group 12 months post surgery.This suggests, in overweight individuals, weight loss is more efficient at improving balance control than increasing, or even maintaining muscle strength. In these individuals, training programs aimed at improving balance control should primarily target weight loss.

Resumen Introduccion El indice de masa corporal (IMC) es el metodo mas practico para medir y comparar la obesidad entre diferentes individuos. El porcentaje perdido del exceso de IMC (PPEIMC) se utiliza para presentar los resultados de los pacientes operados y se basa en la premisa de que un IMC de 25 es el objetivo final, al ser el limite superior de individuos normales. Alcanzar un IMC de 25 es posible en pacientes obesos morbidos con IMC inicial bajo ( Objetivo El objetivo de este trabajo es buscar por metodos estadisticos una formula, basada en hechos clinicos, que identifique el IMCE de acuerdo con el IMC inicial. Pacientes y metodo Se ha analizado el IMC inicial y final de un grupo de 135 pacientes operados de obesidad morbida con la tecnica del cruce duodenal con un seguimiento superior a 3 anos. Se ha utilizado un metodo estadistico de regresion lineal para obtener una formula que calcule el IMCE de cada paciente operado. Resultado Se ha obtenido un algoritmo en el que el IMCE=IMC inicial×0,33+14. Si se aplicaba el IMCE individualizado en vez de la constante del IMC de 25, el PPEIMC mediano era de 99,48 (rango: 76,75 a 110,46). Conclusion Este resultado evidencia que la aplicacion individual del IMCE estima con mayor fiabilidad el exito o fracaso de las operaciones bariatricas.

This was a retrospective study, performed 10 years after surgery, to compare the results between biliopancreatic diversion (BPD) with distal gastrectomy (DG) versus BPD with duodenal switch (DS).Complete follow-up data were available for 96% of patients, allowing a comparison of weight loss, revision, side effects, and complications at 10 years.After BPD-DS, weight loss was 25% greater than after BPD-DG (46.8 +/- 21.7 kg versus 37.5 +/- 22 kg, respectively; P.0001). The need for revision decreased from 18.5% to 2.7% (P.0001), and the prevalence of vomiting during the previous month was 50% less (23.7-50.6%, P.0001) after BPD-DS compared with after BPD-DG. Late complications were the same for both procedures. Blood analysis showed that, after BPD-DS, the levels of calcium, iron, and hemoglobin were significantly greater and the parathyroid hormone level was lower than after BPD-DG (71.3 +/- 44.2 versus 103.0 +/- 64.0 ng/L, respectively; P.0001).The DS greatly improved the BPD, as it was initially proposed. The use of the DS increased weight loss, decreased the need for revision, resulted in fewer side effects, and improved the absorption of nutrients.

Decrease in fat mass and fat-free mass have been observed with weight loss induced by a dietary intervention or surgery. There are concerns that fat-free mass decrease could have some negative functional consequences. The aim of this study was to examine how weight loss affects strength and force control in obese and morbidly obese men.Weight loss was obtained in obese individuals by a hypocaloric diet program until resistance to lose fat and in morbidly obese individuals by bariatric surgery. Maximal force was measured for upper and lower limb and the ability to maintain 15% and 40% of that force. These measures were taken at baseline, in those dieting once resistant to weight loss and 1 year after surgery for those operated on. Normal weight individuals used for control were evaluated twice (6 to 12 months apart).At baseline, there was no significant difference between groups for maximal forces and capabilities to maintain force levels. Weight loss averaged 11.1% of the initial body weight after dieting and 46.3% 1 year after surgery. At the same time, there was for the lower limb a loss of 10.1% in maximal force after dieting and 33.5% after surgery. For the upper limb, there was no change in maximal force after dieting whereas a decrease of 14.4% was observed after surgery. When transformed in force related to body weight, there was no change in relative force for the lower limb after dieting whereas an increased relative force after surgery. There was no significant difference for the ability for maintaining force levels.Despite a large force loss, particularly for the lower limbs in morbidly obese individuals after surgery, this loss is relatively well tolerated because the relation between force and body weight is even improved and the ability to maintain that force is preserved.

Background: The present retrospective study aims to provide additional evidence supporting the fact that waist circumference, in severe obesity, is not a good clinical marker to identify individuals with the metabolic syndrome or an altered metabolic profile. Methods: Relationships between waist circumference and metabolic profile of pre- (n=165) and postmenopausal (n=43) severely obese women were compared to associations observed in pre- (n=52) and postmenopausal (n=35) moderately obese women. Results: Results showed that abdominal obesity assessed by waist circumference was more highly correlated with fasting glycemia, HDL-cholesterol and the cholesterol/HDL-cholesterol ratio in moderately than in severely obese women, before menopause. After menopause, waist circumference was not a valuable predictor of metabolic abnormalities in both groups. Moreover, when waist circumference was included as a criterion of the metabolic syndrome (as defined by the NCEP ATP III guidelines) in severely obese women, the prevalence of this metabolic condition was over-estimated by 72%. Conclusion: These results emphasize the uselessness of waist circumference to assess the prevalence of the metabolic syndrome or an altered metabolic profile in severely obese women.

We examined omental and subcutaneous adipose tissue adipocyte size, and lipolysis and lipoprotein lipase (LPL) activity in a sample of 33 men aged 22.6 to 61.2 years and with a body mass index ranging from 24.6 to 79.1 kg/m2. We tested the hypothesis that lipolysis rates would be higher in the omental fat depot than in subcutaneous adipose tissue and that this difference would persist across the spectrum of abdominal adiposity values. Omental and subcutaneous adipose tissue samples were obtained during surgery. Adipocytes were isolated by collagenase digestion. Adipocyte size and LPL activity as well as basal, isoproterenol-, forskolin-, and dibutyryl cyclic adenosine monophosphate-stimulated lipolysis were measured. Although adipocytes from both fat compartments were larger in obese subjects, no difference was observed in the size of omental vs subcutaneous fat cells. Lipoprotein lipase activity, expressed as a function of cell number, was significantly higher in omental than in subcutaneous fat tissue (P

Despite well-established variations in the health risks posed by visceral vs. subcutaneous abdominal (SCABD) fat depots, surprisingly little is known on the differences within a given adipose tissue (AT) among severely obese patients displaying varying metabolic dysfunction. We thus compared, by quantitative PCR, the expression profile of a number of genes in the SCABD, omental (OME), and mesenteric (MES) depots of severely obese women with (DYS; n = 25) or without (NDYS; n = 23) a dysmetabolic profile. Fasting insulinemia and HOmeostasis Model Assessment-insulin resistance (HOMA-IR) were higher and plasma adiponectin level lower in DYS women (p

Maternal obesity and excess gestational weight gain with compromised metabolic fitness predispose offspring to lifelong obesity and its comorbidities. We demonstrated that compared to offspring born before maternal gastrointestinal bypass surgery (BMS) those born after (AMS) were less obese, with less cardiometabolic risk reflected in the expression and methylation of diabetes, immune and inflammatory pathway genes. Here we examine relationships between gestational obesity and offspring gene variations on expression levels. Methods Whole-genome genotyping and gene expression analyses in blood of 22 BMS and 23 AMS offspring from 19 mothers were conducted using Illumina HumanOmni-5-Quad and HumanHT-12 v4 Expression BeadChips, respectively. Using PLINK we analyzed interactions between offspring gene variations and maternal surgical status on offspring gene expression levels. Altered biological functions and pathways were identified and visualized using DAVID and Ingenuity Pathway Analysis. Results Significant interactions (p ≤ 1.22x10-12) were found for 525 among the 16,060 expressed transcripts: 1.9% of tested SNPs were involved. Gene function and pathway analysis demonstrated enrichment of transcription and of cellular metabolism functions and overrepresentation of cellular stress and signaling, immune response, inflammation, growth, proliferation and development pathways. Conclusion We suggest that impaired maternal gestational metabolic fitness interacts with offspring gene variations modulating gene expression levels, providing potential mechanisms explaining improved cardiometabolic risk profiles of AMS offspring related to ameliorated maternal lipid and carbohydrate metabolism.

Mature adipocytes can reverse their phenotype to become fibroblast-like cells. This is achieved by ceiling culture and the resulting cells, called dedifferentiated fat (DFAT) cells, are multipotent. Beyond the potential value of these cells for regenerative medicine, the dedifferentiation process itself raises many questions about cellular plasticity and the pathways implicated in cell behavior. This work has been performed with the objective of obtaining new information on adipocyte dedifferentiation, especially pertaining to new targets that may be involved in cellular fate changes. To do so, omental and subcutaneous mature adipocytes sampled from severely obese subjects have been dedifferentiated by ceiling culture. An experimental design with various time points along the dedifferentiation process has been utilized to better understand this process. Cell size, gene and protein expression as well as cytokine secretion were investigated. Il-6, IL-8, SerpinE1 and VEGF secretion were increased during dedifferentiation, whereas MIF-1 secretion was transiently increased. A marked decrease in expression of mature adipocyte transcripts (PPARγ2, C/EBPα, LPL and Adiponectin) was detected early in the process. In addition, some matrix remodeling transcripts (FAP, DPP4, MMP1 and TGFβ1) were rapidly and strongly up-regulated. FAP and DPP4 proteins were simultaneously induced in dedifferentiating mature adipocytes supporting a potential role for these enzymes in adipose tissue remodeling and cell plasticity.

Background: In order to evaluate the impact of severe obesity and its treatment on quality of life (QoL), it would be important to first identify the areas of QoL most likely to be affected by the disease. Methods: We first constructed a list of 187 items potentially related to QoL of patients with morbid obesity. From this list, consecutive candidates for bariatric surgery were asked to identify what they felt were the most significant items and to grade their importance. The item impact was determined from the proportion of patients who identified it as important, and the mean importance score attributed to this item (impact score = frequency X importance). Results: 100 patients (68 female; mean body mass index 51.5 kg/m2; mean age 42) were interviewed. Overall, the impact of morbid obesity was more important in women than in men. The areas of impairment were very similar in both groups, with the important difference that women ranked their dissatisfaction with physical appearance higher than men. The items having the most important impact on QoL clustered into 7 domains: 1) activity/mobility; 2) symptoms; 3) personal hygiene/clothing; 4) emotions; 5) social interactions; 6) sexual life; and 7) eating behavior. Conclusion: The impact of morbid obesity on QoL is not limited to the activity/mobility domain. Morbid obesity contributes to the impairment of all domains of what is usually referred to as "health-related quality of life".

Background: Obesity is well known to be associated with an increased prevalence of metabolic complications. Severe obesity is thus expected to have more important alterations of the metabolic profile than moderate obesity. This study aimed to compare the metabolic profile of pre- and postmenopausal severely obese women with moderately obese women. Methods: First, the metabolic profile of pre- (n=165) and postmenopausal (n=43) severely obese women (body mass index (BMI) ≥40 kg/m2) was compared to that of pre- (n=52) and postmenopausal (n=35) moderately obese women (BMI of 30-40 kg/m2). Thereafter, pre- and postmenopausal severely obese women were divided into two subgroups according to the presence/absence of a dysmetabolic profile. We used for comparison, a group of pre- and postmenopausal moderately obese women without a dysmetabolic profile. Results: The metabolic profile of pre- and postmenopausal severely obese women was less deteriorated than expected when compared to moderately obese women. Moreover, severely obese women with or without a dysmetabolic profile displayed comparable or even lower plasma levels of cholesterol, HDL and LDL-cholesterol, and a lower cholesterol/HDL-cholesterol ratio than moderately obese women (P≤0.05). After menopause, the metabolic profile of severely obese women, dysmetabolic or not, was similar to that of moderately obese women. Blood pressure was, however, higher in severely obese women compared to moderately obese women, only before menopause (P≤0.0001). Conclusion: These results indicate that despite their large accumulation of adipose tissue, most of the severely obese women had a metabolic profile less deteriorated than expected, when compared to moderately obese women.

This study was carried out to determine the effects of the biliopancreatic diversion (BPD), a bariatric surgery applied to the treatment of morbidly obese humans, on energy balance in rats. BPD was performed on a group of male Wistar rats. Body weight and food intake were measured daily throughout the study. Feces were also collected to assess energy losses and the determination of digestible energy. Energy expenditure and body composition were also determined for the 50-day length of the protocol. On the day of killing, the brain, the entire intestinal tract and white and brown adipose tissues were collected and weighed. Expression of neuropeptide Y (NPY) and agouti-related protein (AgRP) in the ARC nucleus were assessed by in situ hybridization. Marked changes in the regulation of energy balance were observed in the BPD-operated rats. A decrease in digestible energy and food intake coupled with an increase in the fecal energy density and protein fecal energy led to an important weight loss in the BPD-operated rats. This weight loss was observed in the loss of fat mass (specifically the white epididymal, inguinal, retroperitoneal and brown adipose tissues). The rats modified their food intake pattern to be able to potentially eat more during the entire day. An increase in the surfaces of all intestinal structures (muscular and mucosal layers) was observed in the BPD-operated rats. The NPY and AgRP expression in the brain were both shown to be greater in the BPD-operated rats than in the control animals. At the beginning of the study, the surgery led to an energy expenditure decrease, which, however, did not persist throughout the study despite the fact that BPD-operated rats exhibited persistent lower fat free masses. BPD led to a noticeable reduction in weight and fat gains in rats, which was in large part owing to a decrease in digestible energy intake led to by the gastrectomy, the intestinal malabsorption inherent to the surgery and to potentially a thermogenesis stimulation that occurred in the second end of the study. The reduction in energy gain occurs despite adaptations to thwart the intestinal malabsorption and the hunger signals from the central nervous system.

Factors influencing the severity of the metabolic syndrome among obese subjects or the conversion to cardiovascular disease or type 2 diabetes (T2D) remain largely unknown, but there is strong evidence for genetic susceptibilities. Peroxisome proliferator-activated receptor-gamma co-activator-1 (PPARGC1) is a transcriptional co-activator of many nuclear receptors including PPAR-gamma, involved in the regulation of fatty acid oxidation, skeletal muscle fiber type specificity, and gluconeogenesis. Given the critical role of PPARGC1, it becomes a promising candidate gene for the metabolic syndrome and T2D. This study aimed to investigate whether genetic variations in human PPARGC1 gene are associated with metabolic syndrome-related phenotypes and T2D among obese subjects. Molecular screening of the PPARGC1 gene in 24 morbidly obese French-Canadians revealed 13 variants. Eight genetic variations were in introns: c.55-27TA, c.234+52CA, c.553-40AG, c.553-11TC, c.757+161TC, c.1793+19CG, c.2141+192GA, and c.2293+146AG, and five were in coding regions: Thr394Thr, Asp475Asp, Gly482Ser, Thr528Thr, and Thr612Met with a relative allele frequency of 18.5, 5.2, 37.0, 42.5, and 6.8%, respectively. Thr394Thr, Asp475Asp, and Thr528Thr were in linkage disequilibrium with the Gly482Ser variant, the only non-synonymous variant with a relative allele frequency of more than 10%. Association studies were performed with the Gly482Ser variant. In non-diabetics, we compared between genotype differences in metabolic syndrome-related traits (waist girth, SBP, DBP, triglycerides, HDL-cholesterol (C), and fasting glucose levels). There was a difference in mean plasma HDL-C concentrations, the Gly/Gly group had lower concentrations than the Gly/Ser group (P0.05). These results suggest that the Gly482Ser polymorphism may explain some of the between-obese variance observed in metabolic syndrome-related traits.

This is to introduce a new test "negative alliesthesia" for measuring satiation after bariatric surgery. It is a test that is well known by physiologists but has never been used clinically. It is based on the observation that repeated pleasant gustatory stimuli turn into unpleasantness in the process of satiation.We measured the time it took for a repeatedly ingested sweet stimulus to become first unpleasant (negative alliesthesia) and then intolerable (satiety). At the same time, we measured the degree of pleasure aroused by the sweet stimulus (hedonic rating). The test was given to 9 patients before and 3 and 6 months after the duodenal switch procedure and in 10 morbidly obese patients, three times, 3 months apart.The test showed that negative alliesthesia and satiety were three times faster after surgery. The negative alliesthesia time decreased from 16.0 +/- 3.9 minutes to 5.7 +/- 1.4 minutes (P0.0004). The satiety time decreased from 26.7 +/- 5.0 minutes to 10.7 +/- 1.3 minutes (P0.001). Finally, the hedonic rating for the sweet stimulus decreased from 78.8% +/- 15.7% to 49.9% +/- 13.0% at 3 months and 39.3% +/- 20.6% at 6 months after surgery, without, however, reaching statistical significance.The duodenal switch modified negative alliesthesia. It is too soon to say what place this test may have in bariatric surgery, but its simplicity and ingenuity are attractive.

Both weight loss and gastrointestinal surgery for obesity can cause liver disease, making their role in the treatment of obesity-related liver disease controversial.Six hundred eighty-nine severely obese women (n=551) and men (n=138), BMI=47+/-9 kg.m(-2) (mean+/-SD), without known liver disease, underwent biliopancreatic diversion (BPD) with liver biopsy. Fourteen patients (2%) had cryptogenic cirrhosis, 11 of whom underwent multiple repeat biopsies. After 38+/-18 kg weight loss, 104 of the 689 patients underwent routine second biopsies during reoperations 41+/-25 months after BPD. All biopsy specimens were graded for steatosis, fibrosis, and inflammation by a blinded hepatopathologist.All 689 patients lost weight accompanied by improvements in the metabolic syndrome. Among the 104 patients who underwent reoperation, severe fibrosis (grade 3-5) decreased in 28 whereas mild fibrosis (grade 1-2) appeared in 42. Increased fibrosis was related to low-normal serum albumin, uncontrolled diarrhea, low intake of alcohol, and menopausal status. Fibrosis and inflammation decreased over time (P.01). The 11 patients with cirrhosis exhibited decreased fibrosis from a mean grade 5 to grade 3, as well as reduced inflammation, Mallory bodies, and glycogenated nuclei. Seven patients had disappearance and 2 regression of nodules and fibrous bridging.The metabolic syndrome of obesity is a determinant of liver fibrosis and cirrhosis, treatable by substantial weight loss after malabsorptive surgery.

This prospective study evaluated bone changes after biliopancreatic diversion (BPD) consisting of a distal gastrectomy, a 250 cm alimentary channel, and a 50 cm common channel. Thirty-three consecutive patients had clinical, biochemical, and bone mineral density analysis before surgery and 4 and 10 years after surgery. Iliac crest bone biopsies and special tests including parathyroid hormone (PTH), 25-hydroxyvitamin D (25-OH-D), 1,25-dihydroxyvitamin D (1,25-OH2-D), bone-specific alkaline phosphatase (BAP), and osteocalcin were obtained at surgery and 4 years postoperatively. Over the years, with close metabolic surveillance, additional calcium and vitamin D were given as indicated. After BPD, serum levels of calcium and vitamin D were decreased and serum levels of PTH, BAP, and osteocalcin were increased. Bone turnover and mineralization were both increased. Mean osteoid volume (P < 0.0007) and bone formation rate in relation to bone volume (P < 0.02) were increased. Static measures of bone were altered as follows: cortical thickness decreased (P < 0.01) and trabecular bone volume increased (P < 0.01). Ten years after surgery, overall bone mineral density was unchanged at the hip and was decreased by 4% at the lumbar spine. Overall fracture risk, based on the Z score, was unchanged. Preoperative factors predicting bone loss included menopause, smoking, and preexisting osteopenia. An elevated level of 1,25-OH2-D was also found to be a predictor of future bone loss (r = 0.40; P < 0.002). After surgery, a greater increase in bone markers and bone turnover was associated with an increased risk of bone loss. Although elevated osteocalcin levels were associated with overall bone loss (r = 0.52; P < 0.002), lower albumin levels were associated only with bone loss at hip level (r = 0.44; P < 0.02), whereas lower calcium levels were associated only with the loss at the lumbar spine (r = 0.39; P < 0.02). Ten years after surgery, bone loss at the hip continued to depend on albumin levels (r = 0.37; P < 0.03). We concluded that bone was relatively tolerant to the metabolic changes due to BPD. Provided that there is close surveillance for metabolic disturbances, the use of appropriate supplements, and the avoidance of malnutrition, the beneficial effects of surgery far outweigh the risk of postoperative bone disease.

The choice of first-stage operation in bilio-pancreatic diversion with duodenal switch (BPD-DS) is controversial. There are no published long-term comparisons of one- and two-stage BPD-DS outcomes. During 2001–2009, among 1,762 patients scheduled for BPD-DS 48 had duodenal switch (DS) and 53 sleeve gastrectomy (SG) as first-stage procedures. We compared prospectively updated outcomes of 42 DS (100 % open) and 49 SG (88 % laparoscopic), 13 of whom completed their second stage, to a control group of 91 patients with open one-stage BPD-DS. One-year mean percent excess weight loss (%EWL) was greater after SG than DS (47 ± 19 vs. 39 ± 13 SD; p = 0.01) with earlier nadir (16 ± 10 vs. 45 ± 30 months; p

Background: Sleeve gastrectomy (SG) was originally performed as the restrictive and acid-reducing part of a biliopancreatic diversion with duodenal switch (BPD-DS). It is now recognized as a stand-alone procedure, but direct comparison between the two procedures is still lacking. The goal of this study is to compare the outcomes of the two procedures and their respective impact on obesity-related comorbidities. Methods: All patients who had a laparoscopic SG (n = 378) or a laparoscopic BPD-DS (n = 422) before 10/2011 were included in this study (n = 800). Data were obtained from our prospectively maintained electronic database and are reported as mean ± standard deviation comparing SG with BPD-DS patients. Results: SG patients were older (48 ± 11 vs. 40 ± 10 years, p < 0.001) with a higher prevalence of comorbidities (type 2 diabetes mellitus in 51 vs. 37%; hypertension 62 vs. 49%; sleep apnea 63 vs. 51%; all p < 0.001). Initial BMI was 48 ± 9 vs. 48 ± 6 (p = 0.8). There was one 30-day mortality in the BPD-DS group, from a pulmonary embolism, for an overall mortality rate of 0.13%. Thirty-day complications occurred in 6 vs. 8% of patients (p = 0.2), including gastric leaks in 4 (1%) vs. 0 patients (p = 0.049). Mean follow-up was 29 ± 10 months. Excess weight loss was 45 ± 14 vs. 62 ± 15% at 6 months, 53 ± 18 vs. 81 ± 14% at 12 months, 53 ± 23 vs. 87 ± 15% at 18 months, 50 ± 19 vs. 86 ± 15% at 24 months and 51 ± 24 vs. 83 ± 16% at 36 months (p < 0.05 for all time points). The surgery induced the remission of type 2 diabetes mellitus in 56 vs. 90% of patients, hypertension in 54 vs. 76% and sleep apnea in 43 vs. 74% (all p < 0.05). In type 2 diabetic patients, fasting plasma glucose decreased by -1.9 mmol/l after SG vs. -2.9 mmol/l after BPD-DS (p < 0.05) and hemoglobin A1C by -1.1 vs. -1.9% (p < 0.05). Conclusion: SG results in a significant 3-year weight loss and remission of comorbidities. BPD-DS provides further improvement of associated comorbidities and can be an option for the management of insufficient weight loss or residual comorbidities following SG.

Because of its hepatic venous drainage, visceral fat accumulation is an important risk factor for obesity-related metabolic complications. Objective: To examine the secretory function of a properitoneal fat, the round ligament (RL) in severely obese women. Methods: Metabolic biomarkers, adipogenic, pro- vs. anti-inflammatory, and prothrombotic characteristics were assessed in the RL adipose tissue (AT), and compared to visceral depots, the omental (OME) and mesenteric (MES) fat, in forty-eight severely obese women (BMI, 54 ± 11 kg/m2), aged 38 ± 9 yrs. Expression of key enzymes involved in lipid metabolism (lipoprotein lipase, LPL; hormone-sensitive lipase, HSL and phosphodiesterase-3B, PDE-3B), and of adipogenic factors (peroxisome proliferator activated receptors-γ1/2, PPAR-γ1/2) was measured by real-time PCR. AT mRNA levels of plasminogen activator inhibitor-1 (PAI-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and adiponectin were also determined. Results: AT-LPL mRNA levels were the highes...